The incidence of lung cancer has been rising over the last half century, although the rate has decreased somewhat over the last decade. The American Cancer Society estimates the number of new cases in 2006 to exceed 174,000. Lung cancer is the leading cause of cancer deaths in the United States among both men and women, claiming more lives than colon, prostate and breast cancer combined.
Non-small cell lung cancer (NSCLC) is the most commonly-diagnosed form of the disease, affecting 4 out of 5 patients. In North America, 75% of patients are present with the early-stage (T1, T2) disease. In most cases, early stage NSCLC can be treated successfully with surgery if the cancer has not spread beyond the chest. Surgical resection is the definitive treatment and lobectomy is the procedure of choice. Lobectomy is the most common type of lung cancer surgery, involving removal of an entire lobe of one lung. For these early stage NSCLC patients, lobectomy yields a 5-year survival rate of 65-77%. Locoregional recurrence occurs in 28% of T1N0 tumors submitted to thoractomy, with the highest initial failure rates detected in the ipsilateral hemithorax. Unfortunately, some patients with this disease are poor candidates for lobectomy due to poor pulmonary health or other medical issues.
Stage I NSCLC patients with compromised cardiopulmonary status may undergo limited surgical resections in an attempt at lung preservation while achieving adequate resection margins. However, lesser resections have been associated with an increased risk of local recurrence, even for small peripheral tumors. Nonetheless, limited resection is viewed as an acceptable alternative for patients with poor physiologic reserve or of advanced age.
Though sublobar resection alone is associated with an increased incidence of post-operative disease recurrence, it is still advocated for high risk patients in the absence of a good alternative. External beam radiation therapy has been used successfully to reduce the risk of local recurrence in these compromised patients. However, external beam radiation therapy further reduces pulmonary function because it generally requires the beam to pass through normal lung to reach the target lesion. Some studies suggest that adding brachytherapy to the regimen can make a dramatic difference in outcomes.
Brachytherapy has a long history of use in the treatment of lung cancer patients. Prior studies have shown improved local control using Iodine permanent implants as a radiation boost for Stage III NSCLC with paraspinal or chest wall involvement. Intraoperative brachytherapy has been shown to be an effective therapeutic modality for patients unable to undergo a surgical lobectomy; it is an alternative to external beam irradiation for patients who cannot tolerate further loss of lung function.
D'Amato et al. at Allegheny General Hospital reported favorable results using a brachytherapy technique to implant 125Iodine seeds for improving local control in patients undergoing thoracoscopic wedge resection for peripheral stage I lung cancer. A series of fourteen patients with non-small cell cancer and significant impairment in cardiopulmonary function having small peripheral solitary pulmonary nodules underwent video-assisted thoracoscopic wedge resection and intraoperative 125Iodine seed brachytherapy. At a mean follow-up of 7 months (range, 2 to 12 months), there were no cases of significant radiation pneumonitis or local recurrence. They concluded intraoperative brachytherapy appears to be a safe and efficient alternative to external-beam radiation therapy when adjuvant radiotherapy is considered following therapeutic wedge resection of stage I (T1N0) lung cancers.
Lee et al. at Tufts New England Medical Center reported the results of limited resection for non-small cell lung cancer and the observed local control achieved with the implantation of 125Iodine brachytherapy seeds. Their series consisted of 35 patients who were deemed not to be candidates for a lobectomy or pneumonectomy due to compromised pulmonary function or cardiac indication. These candidates underwent wedge resection (32 patients), segmental resection (2 patients) and lobectomy (1 patient). All patients received 125Iodine seed placement along the resection margin to deliver a dose of 125 to 140 Gy at a 1-cm depth. Their results suggest that limited resection is a reasonable alternative to nonoperative management of lung cancers for compromised patients, particularly those with stage IA lung cancers. The implantation of 125Iodine brachytherapy seeds is effective in reducing the recurrence at the resected lung margin.
Birdas et al. reported further on the work of the Allegheny General Hospital group. They had previously shown that intraoperative brachytherapy decreased the local recurrences associated with sublobar resections for small stage IA NSCLC. In this report, they presented the outcomes of sublobar resection with brachytherapy compared with lobectomy in patients with stage Ib tumors. They retrospectively reviewed 167 stage IB NSCLC patients: 126 underwent lobectomy and 41 sublobar resection with 125Iodine brachytherapy over the resection staple line. Endpoints were perioperative outcomes, incidence of recurrence, and disease-free and overall survival. Patients undergoing sublobar resections had significantly worse preoperative pulmonary function. Hospital mortality, nonfatal complications, and median length of stay were similar in the two groups. Median follow-up was 25.1 months. Local recurrence in sublobar resection patients was 2 of 41 (4.8%), similar to the lobectomy group: 4 of 126 (3.2%; p=0.6). At 4 years, both groups had equivalent disease-free survival (sublobar group, 43.0%; median, 37.7 months; and lobectomy group, 42.8%; median 41.8 months, p=0.57) and overall survival (sublobar group, 54.1%; median, 50.2 months; and lobectomy group, 51.8%; median, 56.9 months; p=0.38). They concluded that sublobar resection with brachytherapy reduced local recurrence rates to the equivalent of lobectomy in patients with stage Ib NSCLC, and resulted in similar perioperative outcomes and disease-free and overall survival, despite being used in patients with compromised lung function. They recommend the addition of intraoperative brachytherapy to sublobar resections in stage Ib patients who cannot tolerate a lobectomy.
These early indications of the efficacy of brachytherapy used in conjunction with sublobular resection for compromised patients have set the stage for a planned national, multi-center clinical trial by the American College of Surgeons Oncology Group and NIH. This Phase III trial, identified as NCT00107172, is currently enrolling patients. These studies and the Phase III clinical trial clearly demonstrate the potential for intraoperative brachytherapy for those non-small cell lung cancer (NSCLC) patients with compromised cardiopulmonary status who are not candidates for lobectomy.
One main problem facing this technique is in the ability to precisely deliver the brachytherapy seeds intraoperatively to achieve the proper dose distribution and minimize the radiation dose to the clinicians performing the procedure.
Under one practice, Pisch et al. have reported on a technique in which loose seeds were manually delivered via a Mick® applicator. Although they did not describe the surgical procedure, they did state that they made multiple passes in the lung parenchyma. Consequently, this procedure would not have been possible through a thoracoscopy port, which would be a potential problem in patients with chronic obstructive pulmonary disease. They also did not discuss seed migration, which would be expected to be a significant issue.
Chen et al. developed an intraoperative technique utilizing vicryl mesh imbedded with 125Iodine radioactive seeds for thoracoscopic placement over the tumor bed and staple line after video-assisted thoracoscopic resection. 125Iodine seeds, spaced 1 cm apart, were embedded into a hollow vicryl suture material. These seeds were attached to a sheet of appropriately sized vicryl mesh with sutures and/or surgical clips at each end. The spacing between rows was adjusted to deliver a dose of 100-120 Gy at 0.5 cm. Radiation protection was achieved during this preparatory step by the use of a custom leaded-plexiglas, autoclavable shield within which the mesh was assembled. The 125Iodine vicryl mesh was then inserted through the thorocoscopy port and sutured over the tumor bed and resection line. As the radioactive mesh was implanted with video assistance over a relatively flat resection surface, it would lay over the surgical bed without any source overlap. Postoperative, orthogonal simulation films were obtained for placement verification and computer dosimetry. Although this procedure solves the problem of seed migration, it presents other difficulties. As shown in the photographs of the paper, delivery of the mesh through the thoracoscopy port is a difficult procedure and one with appreciable dose to the physician. Proper positioning of the mesh in relation to the surgical margin is critical and difficult. Because the seeds are secured in the mesh prior to insertion, they rely on the proper positioning of the mesh in relation to the target to achieve the desired dose distribution. FIG. 1 illustrates this mesh/seed arrangement.
Lee et al. have reported on a technique that solves some of these problems. In this technique, patients undergoing wedge resection have an incision as small as possible, sometimes as small as 5 cm in length. The resection is carried out using either a linear gastrointestinal stapler or an endostapler. They intend to achieve a minimum gross margin>1 cm around the tumor.
Strands of ten 125Iodine brachytherapy seeds, embedded in polyglactin 910 suture with 1 cm spacing were affixed along the resection margin or 0.5 cm on either side of the margin, depending upon the source strength, length of the resection margin, and the number of seeds available. In most cases, from one to three strands were affixed on both sides of the resection margin over its entire length, utilizing interrupted sutures of 3-0 silk spaced approximately 2 cm apart. Whenever an insufficient number of seeds were available to cover the entire resection margin with parallel strands, the most peripheral portion of the resection margin was affixed with a single strand, and the more central portion affixed with parallel strands on either side of the stapled margin. FIG. 2 shows an example of this technique. Source strength was chosen to deliver a combined radiation dose of 125-140 Gy at a depth of 1 cm. FIG. 2 shows a portion of lung in which a wedge resection has previously been carried out. Each limb of the wedge resection is approximately 6 cm in length. Shown is how two multi-seed strands would be affixed to the margin. The most peripheral seeds are placed directly in the margin, and the deeper portions of the wedge have two strands of seeds affixed to the lung spaced approximately 1 cm apart or 0.5 cm from the resection margin. Simple 3-0 silk sutures may be used to hold the strands in place.
This technique has a better possibility of positioning the seeds at the appropriate position relative to the resection margin. However, the radiation dose to the hands of the radiation oncologist/surgeon is significant. Even through the use of relatively thin lead gloves, the reduction in dose is limited. The use of thicker, more heavily shielded lead gloves limits the dexterity sufficiently as to be impractical.
To address this problem, Pisch et al. have reported on an evaluation of the feasibility of using the da Vinci robotic system (Intuitive Surgical) for radioactive seed placement in the wedge resection margin. Their study was of pigs' lungs. Video-assisted thoracoscopic wedge resection was performed in the upper and lower lobes in pigs. Dummy 125Iodine seeds embedded in absorbable sutures were sewn into the resection margin with the aid of the da Vinci robotic system without complications. In the “loop technique,” the seeds were placed in a cylindrical pattern; in the “longitudinal,” they were above and lateral to the resection margin. Orthogonal radiographs were taken in the operating room. Calculated doses at 1 cm ranged from 70 Gy to 107 Gy depending upon the technique. They concluded that robotic technology allows direct placement of radioactive seeds into the resection margin by endoscopic surgery. It overcomes the technical difficulties of manipulating in the narrow chest cavity. With the advent of robotic technology, new options in the treatment of lung cancer, as well as other malignant tumors, will become available. However, this is a complicated and expensive solution.
Other prior art is shown in U.S. Pat. No. 5,906,573 to Aretz and U.S. Pat. No. 6,264,599 to Slater et al. The Aretz '573 patent describes a radioactive surgical fastening device in which a radioisotope is incorporated by ion implantation. The Slater et al '599 patent describes radioactive therapeutic seeds which have means for engaging the tissue surrounding the seeds when the seeds are implanted. Although these patents disclose the concept of associating a radioactive source with a fastener, none of these prior art references teach incorporating a radioisotope into a fastener that is used in the actual surgical procedure, particularly as part of a surgical staple. In, for example, the Slater et al '599 patent they describe the use of an engagement means for positioning therapeutic seeds, however, their engagement means is positioned independent of any surgical operation and is not intended for use as a means for conducting any pair of a surgical procedure.
Accordingly, it is an object of the present invention to provide an apparatus or device for incorporating a radioactive source into or with a surgical procedure means such as a surgical staple so that the radioactive source can be positioned concurrently with the application of the surgical tissue securing means.